Regression of glomerular injury by losartan in experimental diabetic nephropathy.
Many features of chronic kidney disease may be reversed, but it is unclear whether advanced lesions, such as adhesions of sclerotic glomerular tufts to Bowman's capsule (synechiae), can resolve during treatment. We previously showed, using a renal ablation model, that the renoprotective effect of the AT-1 receptor blocker, losartan, is dose-dependent. Here we determined if moderate and advanced glomerular lesions, associated with streptozotocin-induced diabetes, regress with conventional or high-dose losartan treatment. Using daily insulin injection for 10 months, we maintained diabetic adult male Munich-Wistar rats in a state of moderate hyperglycemia. Following this period, some rats continued to receive insulin with or without conventional or high-dose losartan for an additional 2 months. Diabetic rats pretreated with insulin for 10 months and age-matched non-diabetic rats served as controls. Mesangial expansion was found in the control diabetic rats and was exacerbated in those rats maintained on only insulin for an additional 2 months. Conventional and high-dose losartan treatments reduced this mesangial expansion and the severity of synechiae lesions below that found prior to treatment; however, the frequency of the latter was unchanged. There was no dose-response effect of losartan. Our results show that regression of mesangial expansion and contraction of sclerotic lesions is feasible in the treatment of diabetes, but complete resolution of advanced glomerulosclerosis may be hard to achieve.
Teles
Flávio
F
Laboratory of Renal Pathophysiology (LIM-16), Renal Division, Department of Clinical Medicine, Faculty of Medicine, University of São Paulo, São Paulo, Brazil.
Machado
Flávia G
FG
Ventura
Bianca H
BH
Malheiros
Denise M A C
DM
Fujihara
Clarice K
CK
Silva
Luís F F
LF
Zatz
Roberto
R
D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology / Q000627:therapeutic use; D049109:Cell Proliferation / Q000187:drug effects; D003928:Diabetic Nephropathies / Q000188:drug therapy* / Q000473:pathology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D006943:Hyperglycemia; D007328:Insulin / Q000008:administration & dosage; D007678:Kidney Glomerulus / Q000187:drug effects / Q000473:pathology*; D019808:Losartan / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D050527:Mesangial Cells / Q000473:pathology; D051381:Rats; D012074:Remission Induction; D016896:Treatment Outcome
D000959:Antihypertensive Agents; D007328:Insulin; D019808:Losartan